Drug free macromolecular therapeutic platforms possess great potential for treatment of several diseases and disorders. For example, the cross-linking of CD20 followed by the induction of apoptosis as described herein can be used to treat several diseases and disorders including B cell malignancies, inflammatory disorders, and auto-immune diseases with B cell involvement.
Non-Hodgkin's lymphoma (NHL) is a prevalent cancer worldwide with a high mortality rate. In 2012, in the United States alone, there were 70,130 new cases of NHL and 18,940 deaths attributed to NHL. About 85% of NHLs are malignancies originating from B-cells while the remaining malignancies are of T cell origin. B-cell NHLs include Burkitt's, diffuse large B-cell, follicular, immunoblastic large cell, precursor B-lymphoblastic, and mantle cell lymphomas. These cancers are generally classified as either indolent or aggressive, and more than 95% of B-cell lymphomas bear the cell surface antigen CD20. Anti-CD20 monoclonal antibodies (mAbs), mainly rituximab, are commonly used immunotherapies for NHL patients. However, the immunotherapy has a low overall response rate (<50% for relapsed/refractory NHL) and can produce rare but lethal side effects (e.g., progressive multifocal leukoencephalopathy). Many researchers have attributed the clinical non-responsiveness and the adverse effects of anti-CD20 monoclonal antibodies to the Fc-induced cellular events.
There is still a scarcity of compositions and methods that are effective in the treatment of B cell malignancies, inflammatory disorders, and auto-immune diseases with B cell involvement. These needs and other needs are satisfied by the present invention.